Interrelations Between Bacterial Infection, Inflammation, and Thrombosis on Biomedical Devices

生物医疗器械上细菌感染、炎症和血栓形成之间的相互关系

• 批准号: 9632568
• 负责人: Eric Kaler
• 金额: $ 26.03万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9632568&HistoricalAwards=false
• 关键词: Interrelations; Between; Bacterial; Infection; Inflammation

9632568 Cooper Clinical infections are one of the greatest problems associated with synthetic implanted devices. Such infections account for more than 45% of hospital infections, associated with indwelling catheters and surgery for joint replacement, and bypass operations. Such infections are also more difficult to treat than conventional infections. With over 200 million intravascular devices sold annually, it is clear that infections associated with biomedical devices pose a huge problem in clinical medicine. Understanding the mechanisms by which the bacteria responsible for such infections adhere to implants and resist antibiotic treatment is an important step in developine materials that resist bacterial growth, and improving therapy for implant-associated infections. The use of plastic materials for implants is not only associated with risk of infection, but also risk of clot formation (thrombosis), and inflammation around the site. Little is known about the specific mechanisms that govern the complex relationships between infections, inflammation, and thrombosis. Factors that may affect this relationship are the surface chemistry of the device, the proteins that may be absorbed from the blood after implantation, and the surface chemistry of the bacteria and blood cells. The focus of this research will be to investigate the cellular adhesion and activation events that infection, inflammation, and thrombosis have in common, and to determine their individual effects on the other processes. Specifically, the influence that protein and cellular components of thrombi (e.g. fibrin and blood platelets) have in mediating bacterial adhesion and colonization on artificial surfaces will be investigated. The effects of adherent bacteria on platelet adhesion and activation will also be studied. Another important factor that will be investigated is the change in the metabolic state of adherent bacteria on thrombi and on implant surfaces. The adhesion, activa tion, and accompanying shape changes of white blood cells in the presence of adherent bacteria on chemically modified polyurethanes will be studied. These studies will primarily be carried out using an automated viedomicroscopy system that allows the direct observation of individual cells interacting with different surfaces over a period of time. The study of cell-surface interactions will be carried out on both glass and polyurethane surfaces, as well as model surfaces of self-assembling monolayers. The information obtained in this work will provide a better understanding of the interrelationship between implanted devices, bacterial infection, inflammation, and thrombosis, an how each process may influence the other. Detailed understanding of the mechanisms that govern these relationships will lead to the development of biomaterials that resist microbial adhesion and proliferation as well as thrombosis. Ultimately, studies such as these are important in improving patient welfare and reducing health care costs. ***

9632568库珀临床感染是与合成植入器件相关的最大问题之一。 这种感染占医院感染的45％以上，与留置导管以及关节置换手术和旁路手术有关。 与常规感染相比，这种感染也更难治疗。 每年出售超过2亿个血管内装置，很明显，与生物医学相关的感染在临床医学上构成了一个巨大的问题。 了解导致这种感染的细菌粘附于植入物和抵抗抗生素治疗的机制是抗细菌生长的开发材料的重要步骤，并改善了植入物相关感染的治疗。 将塑料材料用于植入物不仅与感染的风险有关，而且还与凝块形成（血栓形成）和该地点周围的炎症有关。 关于控制感染，炎症和血栓形成之间复杂关系的特定机制知之甚少。 可能影响这种关系的因素是设备的表面化学，植入后可以从血液中吸收的蛋白质以及细菌和血细胞的表面化学。 这项研究的重点是研究感染，炎症和血栓形成的细胞粘附和激活事件，并确定它们对其他过程的影响。 具体而言，将研究血栓的蛋白质和细胞成分（例如纤维蛋白和血小板）在介导细菌粘附和定殖对人工表面的介导。 还将研究粘附细菌对血小板粘附和激活的影响。 将要研究的另一个重要因素是在血栓和植入物表面上粘附细菌的代谢状态的变化。 将研究在化学修饰的聚氨酯上存在粘附细菌的粘附，激活和伴随的白细胞的形状变化。 这些研究将主要使用自动viyomicroscopicy System进行，该系统允许在一段时间内直接观察与不同表面相互作用的单个细胞。 细胞表面相互作用的研究将在玻璃和聚氨酯表面以及自组装单层的模型表面上进行。 在这项工作中获得的信息将更好地理解植入设备，细菌感染，炎症和血栓形成之间的相互关系，这是每个过程如何影响彼此的。 对控制这些关系的机制的详细理解将导致抗微生物粘附和增殖以及血栓形成的生物材料的发展。 最终，这样的研究对于改善患者福利和降低医疗保健成本很重要。 ***